title: Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors.
abstract: Primary cilia are displayed during the G(0)/G(1) phase of many cell types. Cilia are resorbed as cells prepare to re-enter the cell cycle, but the causal and molecular link between these two cellular events remains unclear. We show that Tctex-1 phosphorylated at Thr 94 is recruited to ciliary transition zones before S-phase entry and has a pivotal role in both ciliary disassembly and cell cycle progression. However, the role of Tctex-1 in S-phase entry is dispensable in non-ciliated cells. Exogenously adding a phospho-mimic Tctex-1(T94E) mutant accelerates cilium disassembly and S-phase entry. These results support a model in which the cilia act as a brake to prevent cell cycle progression. Mechanistic studies show the involvement of actin dynamics in Tctex-1-regulated cilium resorption. Tctex-1 phosphorylated at Thr 94 is also selectively enriched at the ciliary transition zones of cortical neural progenitors, and has a key role in controlling G(1) length, cell cycle entry and fate determination of these cells during corticogenesis.
authors.affiliation: Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Li
authors.forename: Masaki
authors.initials: M
authors.lastname: Saito
authors.forename: Jen-Zen
authors.initials: JZ
authors.lastname: Chuang
authors.forename: Yun-Yu
authors.initials: YY
authors.lastname: Tseng
authors.forename: Carlos
authors.initials: C
authors.lastname: Dedesma
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Taku
authors.initials: T
authors.lastname: Kaitsuka
authors.forename: Ching-Hwa
authors.initials: CH
authors.lastname: Sung
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000502:physiology*
chemical_list: C533376:DYNLT1 protein, human; D011993:Recombinant Fusion Proteins; D004398:Dyneins